The long term objective of this project is to improve the practicality of anti-idiotype therapy of human B cell leukemias and lymphomas. As specific means for attaining this objective, the project will be carried out in three phases. The first phase will study the practicality of isolating human idiotypic immunoglobulin (IdIg) directly from clinical specimens of lymphoma by detergent lysis of the cells followed by immobilization of IdIg on an immunosorbent made with microcrystalline cellulose or Sepharose. In the second phase, a novel immunization scheme developed in this laboratory will be used in an attempt to increase greatly the yield of anti-idiotype specific antibodies. The immunization protocol utilizes hyperimmunization of weanling mice with particulate antigen, which in this case is IdIg immobilized on the immunosorbent beads. A simplified hybridoma screening system that incorporates immobilized IdIg as the target in a photometric enzyme-linked immunoassay will be used. Finally, the panel of anti-idiotypic antibodies generated by this study will be screened against our large collection of cryopreserved lymphomas to characterize their specificities and possible cross-reactivities. It is hoped that this study will result in a streamlined and more practical procedure for the routine therapeutic production of anti-idiotype monoclonal antibodies.